SMALL MOLECULE THERAPY FOR ALZHEIMER'S DISEASE

DESCRIPTIONprovided by applicantAlzheimer s diseaseADrepresents a progressive degenerative illness that affects the brainresulting in memory impairmentThe complex etiology of AD is not fully resolvedalthough toxic isoforms of amyloidAplaques are strongly implicatedCurrent treatment options are considered to be symptomaticThey are only moderately effective in stabilizing or improving cognitive and functional symptomsMajority of the research into treatment for Alzheimer s focused on the protein beta amyloidwhich is the main component of deposits found in the brain of Alzheimer s sufferersUnfortunately in the pastmany anti amyloid drugs failed in advanced stages due to safety or efficacy concernsThusthere is an unmet need for therapies that halt or substantially slow disease progressionOver the past decadeour continued research has yielded a system to treat ADOur treatment strategy is based on the observation that Apeptides are in a dynamic equilibrium between the periphery and central nervous systemCNSOur lead candidate"Amytrap"is composed of a retro inverso peptideRIPthat can sequester toxicamyloid peptides Aand Ain the peripherythereby drawing these toxic peptides out of the CNSOur research studies have demonstrated theproof of principleof this sequestration effect in vitro and in vivoThe research focused on evaluating the binding capacity of different RI peptidesAmytrap with different peptide sequencesto peptides Aand Ain vitro along with its effects on clearance of plaques from the brain in an AD mouse modelThe results show that Amytrap is able to reduce Alevels in brain extracts from AD model miceThe reduction in Alevels was associated with improved memory parameters in these miceFurther we have observed suggestive evidence that administration of Amytrap to AD mice at younger age is more effectiveThis important piece of observation is consistent with the recent findings resulting fro failed re emerging human clinical trialsWe have further improved the properties of this Amytrap system by linking the RIP to albuminOne of the advantages of the albuminized peptide is the absence of any untoward immune reactionsRecentlywe have obtained additional evidence via imaging experiments that Amytrap does not cross the BBB thus reassuring our peripheral sink hypothesisHoweverAmytrap warrants further investigation to test its potential as a disease modifying agentIn this phaseapplicationwe attempt the next logical decision making pointWe propose to conduct expanded studies on efficacygenetic toxicology and safety pharmacology of the Amytrap moleculeStudies will focus on understanding the properties of Amytrap and translating them to practical applications which will enable us to commercialize AmytrapDetermining the minimum and maximum effective dose of the Amytrap molecule on performance in the "y" maze is one of our primary goals that will result in a therapeutic indexWe plan to examine the genotoxic potential of Amytrap by standard experiments in vitro and in vivoWe will consequently conduct safety pharmacology studies and evaluate the effect of Amytrap on the CNSrespiratory and cardiac systems over long termWe believe Amytrap is ideally positioned in that it closely resembles its biological targetFurtherAmytrap is safe and economical with no side effectsThereforewe anticipate that Amytrap will be accepted in humansThe proposed commercialization plan includes a strong research teamincluding a CROwell verse with IND enabling studiesa comprehensive business plan and commitments from potential strategic partners including Connecticut Innovations IncCIIand BioPharma Strategy AdvisorsCATo this effectCII has already awarded a small grant to RT to fund efforts to bridge the phasewith the phaseresearchThe outcome of the proposed phasestudies is expected to satisfy mandatory requirements to position Amytrap for a future investigative new drugINDfiling and subsequent human clinical testing